Variant chr9-111578941-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001146108.2(PTGR1):c.506T>C(p.Val169Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00265 in 1,591,028 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0027 ( 9 hom. )

Consequence

PTGR1
NM_001146108.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.90

Variant links:

Genes affected

PTGR1 (HGNC:18429): (prostaglandin reductase 1) This gene encodes an enzyme that is involved in the inactivation of the chemotactic factor, leukotriene B4. The encoded protein specifically catalyzes the NADP+ dependent conversion of leukotriene B4 to 12-oxo-leukotriene B4. A pseudogene of this gene is found on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]

PTGR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033938885).

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGR1	NM_001146108.2 linkuse as main transcript	c.506T>C	p.Val169Ala	missense_variant	7/10	ENST00000407693.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGR1	ENST00000407693.7 linkuse as main transcript	c.506T>C	p.Val169Ala	missense_variant	7/10	1	NM_001146108.2	P1	Q14914-1

Frequencies

GnomAD3 genomes

AF:

0.00175

AC:

260

AN:

148392

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000974

Gnomad AMI

AF:

0.00552

Gnomad AMR

AF:

0.000687

Gnomad ASJ

AF:

0.000292

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000988

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00300

Gnomad OTH

AF:

0.000985

GnomAD3 exomes

AF:

0.00129

AC:

295

AN:

228708

Hom.:

AF XY:

0.00120

AC XY:

149

AN XY:

124114

show subpopulations

Gnomad AFR exome

AF:

0.000769

Gnomad AMR exome

AF:

0.000782

Gnomad ASJ exome

AF:

0.000112

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000142

Gnomad NFE exome

AF:

0.00233

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.00274

AC:

3958

AN:

1442534

Hom.:

Cov.:

AF XY:

0.00260

AC XY:

1865

AN XY:

717508

show subpopulations

Gnomad4 AFR exome

AF:

0.000658

Gnomad4 AMR exome

AF:

0.000831

Gnomad4 ASJ exome

AF:

0.000237

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000283

Gnomad4 NFE exome

AF:

0.00343

Gnomad4 OTH exome

AF:

0.00150

GnomAD4 genome

AF:

0.00174

AC:

259

AN:

148494

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

117

AN XY:

72208

show subpopulations

Gnomad4 AFR

AF:

0.000972

Gnomad4 AMR

AF:

0.000686

Gnomad4 ASJ

AF:

0.000292

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000988

Gnomad4 NFE

AF:

0.00299

Gnomad4 OTH

AF:

0.000975

Alfa

AF:

0.00231

Hom.:

Bravo

AF:

0.00179

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00326

AC:

ExAC

AF:

0.00116

AC:

141

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2022

The c.506T>C (p.V169A) alteration is located in exon 7 (coding exon 6) of the PTGR1 gene. This alteration results from a T to C substitution at nucleotide position 506, causing the valine (V) at amino acid position 169 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.74

T;.;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.034

T;T;T

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.5

M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Uncertain

0.43

Sift

Benign

0.073

T;T;T

Sift4G

Benign

0.081

T;T;T

Polyphen

0.99

.;D;D

Vest4

0.75

MVP

0.45

MPC

0.47

ClinPred

0.15

GERP RS

5.0

Varity_R

0.58

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over